The manner in which different pharmacological agents utilize or depend upon cellular Ca ions sites or stores for the initiation and maintenance of contractile responses in vascular smooth muscle will be examined. Conventional techniques will be employed for measurement of isometric tension responses, for 45Ca uptake and rapid washout, and for total Ca ions, Na ion and K ion concentrations. Experiments will be designed to elucidate the manner in which the actions of different stimulatory agents depend upon cellular Ca ions sites or stores as well as the nature of 45Ca uptake and retention. This information could provide a basis for evaluation of ideas concerning the mechanisms by which membrane-bound Ca ions is involved in events leading to alterations in contractile tone. An attempt will be made to characterize the relative importance of affinity for binding sites and of the number of binding sites in rabbit and rat aortic smooth muscle. In addition, the distribution of 14C-gentamicin will be characterized in rabbit aortic smooth muscle and the nature of gentamicin-Ca ions interactions studied. The effects of selected divalent ions (e.g., Mn ions, Cd ions) on intracellular 45Ca binding will be examined, and the effects of phosphatidyl serine and Ca ions ionophores on 45Ca distribution in vascular and ileal smooth muscle will be compared. Thus, information will be obtained concerning the cellular actions of a variety of ions and drugs in isolated vascular smooth muscle preparations. BIBLIOGRAPHIC REFERENCES: A paper on "Negative inotropic effects of gentamicin in guinea pig left atria" by F.R. Goodman and H.R. Adams was presented at the 1976 FASEB meeting (April, 1976) and included in Fed. Proc. 35: 613, 1975. A paper on "Comparison of uptake and binding of disodium cromoglycate and phenol red in rat lung" by T.H. Gardiner and F.R. Goodman was presented at the 1976 FASEB meeting (April, 1976) and included in Fed. Proc. 35: 327, 1976.